Neutrophil crawling in capillaries; a novel immune response to Staphylococcus aureus.
PLoS Pathog
; 10(10): e1004379, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-25299673
ABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA), particularly the USA300 strain, is a highly virulent pathogen responsible for an increasing number of skin and soft tissue infections globally. Furthermore, MRSA-induced soft tissue infections can rapidly progress into life-threatening conditions, such as sepsis and necrotizing fasciitis. The importance of neutrophils in these devastating soft tissue infections remains ambiguous, partly because of our incomplete understanding of their behaviour. Spinning disk confocal microscopy was used to visualize the behaviour of GR1-labelled neutrophils in subcutaneous tissue in response to GFP-expressing MRSA attached to a foreign particle (agarose bead). We observed significant directional neutrophil recruitment towards the S. aureus agarose bead but not a control agarose bead. A significant increase in neutrophil crawling within the capillaries surrounding the infectious nidus was noted, with impaired capillary perfusion in these vessels and increased parenchymal cell death. No neutrophils were able to emigrate from capillaries. The crawling within these capillaries was mediated by the ß(2) and α(4) integrins and blocking these integrins 2 hours post infection eliminated neutrophil crawling, improved capillary perfusion, reduced cell death and reduced lesion size. Blocking prior to infection increased pathology. Neutrophil crawling within capillaries during MRSA soft tissue infections, while potentially contributing to walling off or preventing early dissemination of the pathogen, resulted in impaired perfusion and increased tissue injury with time.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Staphylococcus aureus
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Infecções Cutâneas Estafilocócicas
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Infiltração de Neutrófilos
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Neutrófilos
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article